Transcriptome analysis of CD14+ monocytes from SSc patients
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ABSTRACT:
PROVIDER: PRJNA662949 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12625502.fastq.gz | Fastqsanger.gz | |||
| SRR12625503.fastq.gz | Fastqsanger.gz | |||
| SRR12625504.fastq.gz | Fastqsanger.gz | |||
| SRR12625505.fastq.gz | Fastqsanger.gz | |||
| SRR12625506.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: To compare transcriptome profile of CD14+ blood monocytes from systemic sclerosis (SSc) patients and healthy controls. Methods: CD14+ monocytes were isolated from peripheral blood of lcSSc (n=5, age=54.4±6.7), dcSSc patients (n=5, age=51.8±7.2) and age- and sex-matched healthy controls (HC) (n=5, age=50.8±9.7). Total RNA was isolated and polyA libraries were prepared using TruSeq Stranded mRNA kit. Next Generation Sequencing was performed using Illumina HiSeq 4000 platform. Differentially expressed genes were computed using DESeq2 algorithm. Results: We detected 1440 differentially expressed genes between dcSSc vs HC and 225 between lcSSc and HC respectively (p≤0.01; log2 ratio≥0.5, Fig 1). Among those, in dcSSc 1076 were upregulated (e.g. MMP9, IL1R2, FLT3, MIF, TLR9) and 364 were downregulated (e.g. TGFBR1, CD44, CD244, HLA-DRA, HLA-G). In lcSSc 160 transcripts were upregulated (e.g. CCL2, WNT5B, MMP17) and 65 were downregulated (e.g. KLF11, IRAK2). We identified 123 commonly deregulated genes between SSc subgroups (e.g. CCL3, CD14, IL27, MMP17). Principal component analysis showed close clustering within SSc subgroups and clear separation from healthy controls. Pathway analysis revealed alterations in several biological processes important in fibrogenesis including antigen presentation, MIF-induced immune responses, TGF-β, NOTCH and WNT signalling pathways. qPCR analysis further confirmed differences in gene expression on mRNA level (n HC=8, n SSc=25, p≤0.05). Conclusions: To our knowledge, this is the first global transcriptome analysis of peripheral blood CD14+ monocytes in SSc. Our results suggest a primary activation of monocytes in peripheral blood, which might be further translated into novel cellular biomarker of the disease and potentially used for distinguishing between responders and non-responders to a novel treatment in future clinical trials.
2021-09-10 | GSE157840 | GEO
Project description:Systemic sclerosis is a multisystem autoimmune disorder that has an unclear etiology and disproportionately affects African Americans (AA). Additionally, monocytes show heightened activation in SSc, and in AA relative to European ancestry (EA) individuals. Monocytes are thus a good target tissue for elucidating disease mechanisms. In this study, we sought to identify differentially expressed genes in classical monocytes from AA SSc patients relative to unaffected AA controls. We performed RNAseq to profile the transcriptome on FACS-isolated classical monocytes (CD14++CD16-) from 16 female AA SSc cases and 18 female AA controls. We observed modest gene expression differences between cases and controls. The genes harboring the top differentially methylated cytosines are enriched for metabolic processes. The relatively modest differences in gene expression observed between patients and controls is consistent with prior evidence of stronger inflammatory signatures in AA.
2022-02-07 | GSE196070 | GEO
Project description:Systemic sclerosis is a multisystem autoimmune disorder that has an unclear etiology and disproportionately affects African Americans (AA). Additionally, monocytes show heightened activation in SSc, and in AA relative to European ancestry (EA) individuals. Monocytes are thus a good target tissue for elucidating disease mechanisms. In this study, we sought to investigate differentially methylated loci in classical monocytes from AA SSc patients and unaffected AA controls. We used Illumina’s MethylationEPIC BeadChip to profile DNA methylation patterns on FACS-isolated classical monocytes (CD14++CD16-) from 12 female AA SSc cases and 12 female AA controls. We observed modest DNA methylation differences between cases and controls. The genes harboring the top differentially methylated cytosines are enriched for immune pathways and metabolic processes. The relatively modest differences in DNA methylation observed between patients and controls is consistent with prior evidence of stronger inflammatory signatures in AA.
2022-02-07 | GSE196007 | GEO
Project description:Bone marrow monocytes are primarily committed to osteoclast formation. It is, however, unknown whether potential primary alterations are specifically present in bone marrow monocytes from patients with multiple myeloma, smoldering myeloma or monoclonal gammopathy of undetermined significance. We analyzed the immunophenotypic and transcriptional profiles of bone marrow CD14+ monocytes in a cohort of patients with different types of monoclonal gammopathies to identify alterations involved in myeloma-enhanced osteoclastogenesis. The number of bone marrow CD14+CD16+ cells was higher in patients with active myeloma than in those with smoldering myeloma or monoclonal gammopathy of undetermined significance. Interestingly, sorted bone marrow CD14+CD16+ cells from myeloma patients were more pro-osteoclastogenic than CD14+CD16-cells in cultures ex vivo Moreover, transcriptional analysis demonstrated that bone marrow CD14+ cells from patients with multiple myeloma (but neither monoclonal gammopathy of undetermined significance nor smoldering myeloma) significantly upregulated genes involved in osteoclast formation, including IL21RIL21R mRNA over-expression by bone marrow CD14+ cells was independent of the presence of interleukin-21. Consistently, interleukin-21 production by T cells as well as levels of interleukin-21 in the bone marrow were not significantly different among monoclonal gammopathies. Thereafter, we showed that IL21R over-expression in CD14+ cells increased osteoclast formation. Consistently, interleukin-21 receptor signaling inhibition by Janex 1 suppressed osteoclast differentiation from bone marrow CD14+ cells of myeloma patients. Our results indicate that bone marrow monocytes from multiple myeloma patients show distinct features compared to those from patients with indolent monoclonal gammopathies, supporting the role of IL21R over-expression by bone marrow CD14+ cells in enhanced osteoclast formation.
2017-04-11 | GSE70345 | GEO
Project description:We detected changes in genes expression in patients with 5q- syndrome in CD14+ monocytes due to treatment with lenalidomide. Total RNA was obtained from CD14+ monocytes from peripheral blood of 6 controls, 6 patients before treatment, and 5 patients during treatment.
2011-09-11 | E-GEOD-31460 | biostudies-arrayexpress
Project description:Background: Circulating periostin levels are increased in systemic sclerosis (SSc) patients and correlates positively with disease severity. Additionally, monocytes/macrophages are one of the key cells in SSc pathogenesis. However, the effect of periostin on immune cells, particularly monocytes and macrophages, has not been well investigated. Objectives: To examine the effect of periostin on monocytes and monocyte-derived macrophages (MDMs) in SSc. Methods: Monocytes were purified from blood samples of nine diffuse cutaneous SSc patients and five healthy controls (HCs) and were differentiated into macrophages. Cell surface markers were assessed by flow cytometry. RNA sequencing analysis was performed on recombinant periostin-stimulated monocytes from three HCs. Cytokine/chemokine and extracellular matrix (ECM) protein expressions in MDMs differentiated supplemented with recombinant periostin were assessed by quantitative real-time polymerase chain reaction and bead-based immunoassays in six HCs. Moreover, we evaluated whether periostin was involved in monocyte migration by Transwell assay. Results: The modified Rodnan total skin thickness score correlated positively with the proportion of CD80-CD206+ M2 cells. The M2 macrophage proportion was reduced in rPn-stimulated MDMs in HCs, but not in SSc patients. mRNA expression levels of pro-fibrotic cytokine, chemokine, and ECM protein genes were significantly upregulated in recombinant periostin-stimulated monocytes and MDMs as compared to those from control monocytes and MDMs. Similar trends for their protein levels were also observed in MDMs. Moreover, the ratio of migrated cells in recombinant periostin-stimulated monocytes was significantly higher than that in control monocytes.
2022-09-22 | GSE213614 | GEO
Project description:The human dendritic cell (DC) family has recently been expanded by CD1c+CD14+CD163+ DCs, introduced as DC3. DC3 are found in tumors and peripheral blood of cancer patients but which cells can serve as their pre-cursors remain unknown. CD1c+CD14+ cells share similarities with both CD1c+ DCs (cDC2s) and CD14+ monocytes on transcriptomic and phenotypic level. To investigate whether CD14+ cDC2s are closer related to CD14- cDC2s or monocytes on transcriptomic level, we analyzed their RNA.
2023-12-01 | GSE218218 | GEO
Project description:To clarify the role of monocyte in the pathogenesis of SSc, we analyzed gene and protein expression in monocyte from SSc and healthy controls in order to identify the molecules which were associated with pathogenesis of SSc.
2013-03-12 | GSE44997 | GEO
Project description:To clarify the role of monocyte in the pathogenesis of SSc, we analyzed gene and protein expression in monocyte from SSc and healthy controls in order to identify the molecules which were associated with pathogenesis of SSc.
2013-03-12 | GSE44996 | GEO
Project description:To clarify the role of monocyte in the pathogenesis of SSc, we analyzed gene and protein expression in monocyte from SSc and healthy controls in order to identify the molecules which were associated with pathogenesis of SSc.
2013-03-12 | GSE44998 | GEO